The Significance of Peritoneal Cytology in Uterine Cervix and Endometrial Cancer

Objective.The purpose of this study was to determine the incidence of positive peritoneal cytology and to elucidate the prognostic value of peritoneal cytology in patients with uterine cervix and endometrial cancer.Materials and methods.The incidence of positive peritoneal cytology was investigated in 642 patients including 339 uterine cervix and 303 endometrial cancers. Survival was estimated by the Kaplan–Meier method in a subgroup of 116 stage II cervix and 199 stage I endometrial cancers, and multivariate analysis using Cox's proportional hazards model was used to identify an independent prognostic factor.Results.The incidence of positive peritoneal cytology was found to be 9% in uterine cervix cancer and 15% in endometrial cancer. The incidence was higher in patients with some clinicopathologic status such as advanced stage, lymph node metastasis, ovarian metastasis, and deeper myometrial invasion. The 5-year survival rate for patients with positive or negative peritoneal cytology was 44 or 80% in stage II cervix cancers and 80 or 92% in clinical stage I endometrial cancers, respectively. Multivariate analysis revealed that independent prognostic determinants were pelvic and paraaortic lymph node metastasis and peritoneal cytology in stage II cervix cancer and peritoneal cytology in stage I endometrial cancer. Proper treatment protocol should be scheduled for patients with positive peritoneal cytology.     

Flow cytometric DNA analysis versus cytology in the evaluation of peritoneal fluids.

The use of flow cytometric DNA analysis as an adjunct to cytology in peritoneal fluid evaluation was studied. One hundred ninety-five fluids from 193 gynecologic patients were subjected to both DNA analysis and cytologic examination. It was found that 117/195 (60%) had invasive malignancies (50 ovarian, 48 endometrial, 17 cervical, and 2 miscellaneous); 34/117 (28%) patients with malignancies were positive by cytology, and 10/117 (8.5%) were positive (aneuploid) by DNA analysis. Of 34 cytologically positive cases, 7 (21%) were DNA positive, 25 (74%) were DNA negative, and in 2 (6%) insufficient cells were obtained. Only 3 fluids (3%) from malignancies were positive by flow cytometry and negative by cytology (1 stage I ovarian cancer, 1 stage I endometrial cancer, and 1 stage III ovarian cancer). No false-positive cytology and one probable false-positive flow result was obtained. If only those patients with histologically documented peritoneal involvement are considered, 29/43 (65%) had positive cytology and 8/43 (19%) had a positive flow result. We conclude that: (1) the high false-negative rate of flow cytometry (79%) versus cytology in this study may be related to a high percentage of diploid cancers, specimen preparation, or histogram interpretation, and (2) flow cytometry rarely adds to cytologic evaluation and is probably best reserved for use only in selected cases.     

Malignant peritoneal cytology as prognostic indicator in stage I endometrial cancer

The prognostic significance of malignant peritoneal cytology was evaluated in 93 patients with stage I endometrial cancer seen at Roswell Park Memorial Institute. Eighty-three patients (89%) had negative cytologic samples and ten (11%) had positive cytology for neoplastic cells. All patients were followed for a minimum of ten years or until dead from cancer or intercurrent disease. No patient received treatment for positive cytology. There was one recurrence in the patients with positive cytology (10%), and six recurrences in the negative group (7%). The actuarial survival rate at five and ten years for patients with negative cytology was 93.9 and 92.5%, respectively. For patients with positive cytology, the survival was 87.5% at both time intervals. No significant difference was found between the groups. Malignant peritoneal cytology does not seem to be a prognostic indicator in stage I endometrial cancer.     

Malignant peritoneal cytology in stage I endometrial adenocarcinoma: the effect of progesterone therapy (a preliminary report)

From February 1982-June 1986, 25 consecutive patients with surgical stage I endometrial adenocarcinoma (no evidence of metastasis at surgery or occult cervical or adnexal involvement on histopathologic review) and malignant peritoneal cytologic washings were treated with progesterone therapy. Twenty-two patients have undergone a second look laparoscopy and repeat cytologic washings, one of those also underwent a third look laparoscopy. Two patients refused second look laparoscopy, and in a third patient laparoscopy was medically contraindicated; all three have no evidence of disease (NED) at 15, 46, and 64 months respectively and are off therapy. Of the 22 patients who underwent second look laparoscopy, 21 (95%) had no macroscopic evidence of recurrent endometrial carcinoma and repeat negative peritoneal cytology; 1 patient (5%) had persistent malignant peritoneal cytology but was NED at third look laparoscopy one year later. All 25 patients are off progesterone therapy and remain clinically NED from 12-64 months. Although progesterone therapy for malignant peritoneal cytology resulted in a 100% reversal of malignant peritoneal cytology to normal in the 22 patients who underwent second or third look laparoscopy and all 25 patients remain clinically NED, the true value of progesterone therapy can only be ascertained by a randomized trial of progesterone versus no therapy.     

Ovarian metastasis in women with clinical stage I endometrial carcinoma

BACKGROUND: The incidence of ovarian metastasis in women with clinical stage I endometrial carcinoma is generally reported to be 5%, leading to the practice of removing the ovaries at surgery even in young patients. METHODS: A retrospective study of 84 patients with clinical stage I endometrial cancer was carried out. Patients were excluded if the pathologic study revealed any evidence of extrauterine, apart from adnexal, spread or if the peritoneal cytology was positive. Patients with serous papillary or clear cell tumor histology were also excluded. RESULTS: Sixty-seven patients fulfilled the inclusion criteria. Only three (4%) patients were found to be in surgical stage IIIA, all three had grade 3 tumors. Of these patients, two had uterine serosal involvement and one had a microscopic tumor implant in a fallopian tube; none had ovarian metastasis. CONCLUSIONS: The risk of ovarian metastasis in women with well to moderately differentiated endometrial cancer, myometrial invasion limited to less than one half of the myometrium, negative peritoneal cytology and no evidence of metastatic lymph node spread is negligible. Young patients with a preoperative histological diagnosis of well to moderately differentiated endometrial carcinoma may be surgically staged, leaving the final decision regarding removal of the ovaries pending a thorough pathological review of the surgical specimens.     

Prognostic value of peritoneal cytology in endometrial carcinoma

To determine whether positive peritoneal cytology is an independent poor prognostic factor in patients with endometrial carcinoma the records of 381 patients were reviewed. Positive peritoneal cytology was found in 24 of 381 (6.3%) patients. In clinical stage I disease, 16 of 322 (5.0%) patients had positive peritoneal cytology. Patients with positive cytology were more likely to have higher-grade tumors and extrauterine disease at the time of surgery (45% vs 2.3%) than were patients with negative cytology. Five-year survival was significantly less for patients with positive cytology than negative (50% vs 81.2%). For patients with surgical stage I disease (no extrauterine spread at surgery) there was no significant difference in 5-year survival between groups with positive and negative cytology (80% vs 86.3%). The majority (70.8%) of patients with endometrial cancer and positive peritoneal cytology have extrauterine disease at the time of surgery. Although overall 5-year survival is less for patients with positive cytology, when other risk factors are controlled for, there is no difference in survival for patients with no demonstrable extrauterine disease despite positive cytology. We conclude that positive peritoneal cytology is not an independent prognostic indicator for patients with endometrial cancer.     

子宫内膜癌手术病理分期的临床意义

目的 探讨子宫内膜癌手术病理分期的临床意义。方法 对我院1995年1月至1999年12月间初治为手术治疗的96例子宫内膜癌患者的临床资料进行回顾性分析,术前采用临床分期术后采用手术病理分期,对这两种分期方法进行比较。结果 两种分期不符合率为45．8％（44／96）,其中临床Ⅰ期为24．0％（12／50）,Ⅱ期76．9％（30／39）,Ⅲ期为5例中2例。盆腔淋巴结转移率为10．3％（8／78）,其中临床Ⅰb期为16例中1例,Ⅱ期14．7％（5／34）。子宫外盆腔转移率14．6％（14／96）,其中临床Ⅰb期为19例中2例,Ⅱ期23．1％（9／39）。卵巢转移率9．4％（9／96）,其中临床Ⅰa期为9．7％（3／31）,Ⅱ期为10．3％（4／39）。腹腔冲洗液细胞学阳性率为7．9％（7／89）,其中临床Ⅰ期为4．0％（2／50）,Ⅱ期为10．3％（4／39）。大网膜转移率5．2％（5／96）,阑尾转移率2．1％（2／96）。经单因素分析,临床分期、子宫肌层浸润深度、病理分级和组织学类型均与盆腹腔转移有关（P＜0．01,0．05）。经多因素相关分析,前3个因素间比较,差异有显著性（P＜0．05）。结论 手术病理分期较临床分期准确,临床分期尤其是临床Ⅱ期的误差率较高,临床处理上应予重视。子宫内膜癌盆腹腔转移与临床分期、子宫肌层浸润深度、病理分级密切相关。手术病理分期能客观判断预后,并指导治疗。Ⅲ     

Prognostic significance of positive peritoneal cytology in endometrial carcinoma

A retrospective review of 280 patients with endometrial carcinoma who had peritoneal cytologic examination done at the time of laparotomy was undertaken. A positive cytologic finding was the only manifestation of extrauterine disease in 16 patients (6%). Four (25%) of these patients had a recurrence. Only 13 (5%) of 237 patients with negative cytologic findings had a recurrence. Positive peritoneal cytology is a marker for potential recurrence.     

Peritoneal cytology in patients with uterine cervical carcinoma.

We studied the relationship between cytological diagnosis of peritoneal washing and pathohistological findings in 97 cases of stage Ib and 103 cases of stage IIa or b cervical carcinoma. No positive cytology was found in 24 cases classified as pT1 by pTNM classification. Positive cytology was found in 8 out of 40 cases with retroperitoneal lymph node metastasis, 2 out of 5 cases with uterine corpus infiltration, and 3 out of 4 cases with ovarian metastasis. Negative cytology was often found even in cases with metastasis to several retroperitoneal lymph nodes, while positive cytology was also found in cases without metastasis. The mechanism of cervical carcinoma metastasizing to retroperitoneal lymph nodes may not be the same as that of spreading into the abdominal cavity. Many cases with positive peritoneal cytology tended to recur with peritoneal carcinoma as compared to those with negative cytology. The above findings indicate that chemotherapy, including intraperitoneal administration, is necessary in addition to radiation therapy for patients with cervical carcinoma with positive peritoneal washings.     

The prognostic significance of peritoneal cytology for stage I endometrial cancer

A retrospective study of 567 patients treated for surgical stage I endometrial cancer was undertaken to resolve the controversy over the significance of malignant peritoneal cytology findings in early-stage disease. Twenty-eight women (4.9%) had peritoneal cytology positive for malignant cells. Comparisons were made between the groups with positive and negative cytology. Subgroups used in analysis included stage according to the International Federation of Gynecology and Obstetrics, treatment regimen, histology, grade, depth of myometrial invasion, and cervical Papanicolaou smear results. Cervical smear status was the only subgroup in which a statistically significant difference was found, with the positive peritoneal cytology patients having a higher incidence of positive Papanicolaou smears (P = .01). Forty-nine women (8.6%) developed recurrent tumor, 7% of the negative-cytology group and 32% of the positive-cytology group (P = .0002). The progression-free survival rate was lowered significantly by positive peritoneal cytology (P less than .0001); patients with negative peritoneal cytology had a significantly better 5-year survival rate, 96 versus 84% (P = .0001). When multivariate analysis was performed on the 477 cases that had no missing values, peritoneal cytology remained significant for both survival rate (P = .01) and progression-free interval (P = .002). Positive peritoneal cytology is a poor prognostic factor for patients with surgical stage I endometrial cancer.     

False-negative peritoneal cytology in metastatic ovarian carcinoma

Seventy-nine laparotomies for disseminated intraperitoneal ovarian carcinoma were reviewed to determine the frequency and possible causes of false-negative peritoneal cytology. Negative peritoneal cytology (defined as any reading other than positive) was found in 16 of 79 cases (20%). False-negative cytology occurred more frequently with peritoneal washings (48%) than with ascites (6%; P less than .001); with second-look surgery (50%) than at primary surgery (12%; P = .004); with peritoneal metastasis less than 0.5 cm (50%) than with metastasis greater than 0.5 cm (16%; P = .02); and with bloody cytology specimens (25%) rather than specimens without blood (0%; P = .06). Volume of peritoneal specimen, architectural grade, cytologic grade, and stage of disease (III versus IV), did not affect the frequency of false-negative cytology. The high prevalence of negative cytology associated with peritoneal washings, small tumor size, and second-look surgery suggests that negative cytology is a result of poor distribution of peritoneal washings and infrequent exfoliation of malignant cells rather than misinterpretation of malignant cells present in cytology specimens.     

子宫内膜癌卵巢转移危险因素的探讨

目的 探讨子宫内膜癌卵巢转移的危险因素及手术中保留卵巢的可行性.方法 回顾性分析1997年1月至2006年12月在江西省妇幼保健院首治为手术治疗的638例子宫内膜癌患者的临床病理资料.结果 36例(5.6%,36/638)患者发生卵巢转移.单因素分析显示,子宫内膜癌卵巢转移的相关因素为病理类型、病理分级、子宫肌层浸润、腹水或腹腔冲洗液细胞学检查阳性、盆腔淋巴结转移、宫旁浸润、腹主动脉旁淋巴结转移、子宫浆膜浸润(P均＜0.05),而年龄、脉管浸润、宫颈浸润与卵巢转移无明显相关性(P均＞0.05).多因素分析显示,子宫内膜癌卵巢转移的独立危险因素按危险强度排列为:盆腔淋巴结转移、腹水或腹腔冲洗液细胞学检查阳性、病理分级.结论 子宫内膜样腺癌、细胞高分化、无盆腔淋巴结转移、无腹主动脉旁淋巴结转移、元肌层浸润、腹水或腹腔冲洗液细胞学检查阴性、年轻的患者可考虑手术中保留卵巢.     

Peritoneal cytology in endometrial cancer: a review

Utilization of literature review to evaluate peritoneal cytology as a test for the detection of malignant cells in the peritoneal cavity is limited by the size of the study populations, varied use of preoperative radiation, the lack of consistent methodology for specimen retrieval and processing, and the inherent subjectivity of cytologic interpretation. A standardized methodology for retrieval and processing of peritoneal cytologic specimens should be developed to allow meaningful comparisons of future studies. However, certain conclusions are permitted from published data: 1. The incidence of positive peritoneal cytology is 11.4 per cent among 3091 patients with FIGO stage I endometrial cancer. 2. The depth of the uterus does not influence the incidence of positive peritoneal cytology. 3. Positive peritoneal cytology is predictive of other known prognostic factors including advanced histologic grade, depth of myometrial invasion, and pelvic/periaortic lymph node metastases. 4. The presence of malignant cells in the peritoneal washings from some patients with no myometrial invasion and the high incidence of lymph node metastases in other patients with positive peritoneal cytology suggest that malignant cells gain access to the peritoneal cavity in a variety of ways. It is unclear whether each of these modes of access result in viable tumor cells with the potential for viable metastasis. The high incidence of lymph node metastasis in such patients suggests that lymphatic dissemination of malignant cells plays a significant role in the development of positive peritoneal cytology. In this setting positive peritoneal cytology clearly identifies that individual at high risk for recurrence.(ABSTRACT TRUNCATED AT 250 WORDS)     

Endometrial carcinoma: the relevance of cervical cytology

In patients with endometrial carcinoma, preoperative identification of poor prognostic factors is helpful in planning therapy. Extended surgical staging, including pelvic and periaortic node dissection, is indicated in patients with deep myometrial invasion or high-grade tumor, or when other risk factors for extrauterine spread are present. In this study, cervical cytology was reviewed in 86 patients with endometrial carcinoma, all of whom underwent surgical staging, to correlate the cytologic results with surgical and pathologic findings. Cervical cytology was normal in 20 patients (23%), whereas suspicious or malignant endometrial cells were present in 23 and 43 cases (27 and 50%), respectively. Suspicious or malignant cervical cytology was associated with deeper myometrial invasion (P = .011), higher postoperative tumor grade (P = .006), positive peritoneal washings (P = .012), and more advanced stage by International Federation of Gynecology and Obstetrics criteria (P = .024). When compared with patients with normal cervical cytology, those who had malignant endometrial cells had over twice the risk of deep myometrial invasion (67 versus 30%), twice the risk of grade 2 or 3 tumor (60 versus 30%), and three times the risk of positive peritoneal washings (33 versus 10%). Seventy-four percent of patients with malignant cervical cytology were stage IC or more. In contrast, 70% of patients with normal cervical cytology were stage IA or IB. Patients with endometrial carcinoma who have malignant endometrial cells detected by cervical cytology are at increased risk of having a deeply invasive, high-grade, advanced-stage tumor, and therefore are more likely to require extended surgical staging.     

宫腔镜检查诊断子宫内膜癌的价值及与腹腔冲洗液阳性的关系探讨

目的:探讨宫腔镜检查对子宫内膜癌的诊断价值,以及是否增加腹腔冲洗液细胞学阳性率。方法:回顾性分析在本院行手术治疗后病理检查确诊为子宫内膜癌患者113例的临床资料,其中术前行单纯分段诊断性刮宫71例(分段诊刮组),行宫腔镜检查后再行分段诊刮42例(宫腔镜组)。比较两组手术前后的诊断、组织学分级、组织学类型符合率,腹腔冲洗液细胞学的阳性率,并同时分析组织学类型、组织学分级、肌层浸润深度、病灶分布、附件转移等与腹腔冲洗液细胞学的关系。结果:宫腔镜组42例患者,病理诊断符合率97.62%(41/42),高于分段诊刮组的病理诊断符合率83.10%(59/71),差异有统计学意义(P<0.05)。宫腔镜组腹腔冲洗液阳性率28.57%(12/42),高于分段诊刮组的阳性率25.35%(18/71),但两组比较差异无统计学意义(P>0.05)。113例子宫内膜癌患者腹腔冲洗液阳性与宫腔病灶范围大小有关(P<0.05),与附件转移、子宫肌层浸润深度、组织学类型、组织学分级无关(P>0.05)。结论:宫腔镜检查诊断子宫内膜癌准确性优于单纯分段诊刮,并且不增加腹腔冲洗液阳性率。腹腔冲洗液阳性率与宫腔病灶范围大小有关。     

Peritoneal cytology in patients with endometrial carcinoma

Peritoneal cytology was obtained in 61 patients with carcinoma of the endometrium at the time of laparotomy. The incidence of positive peritoneal cytology was 23.0%. It increased as the clinical stage advanced. The incidence of positive peritoneal cytology in patients with well-differentiated carcinoma or superficial myometrial invasion was low. The rate of paraaortic lymph node metastasis was higher in patients with positive peritoneal cytology than in patients with negative peritoneal cytology. However, this trend was not recognized in pelvic lymph node metastasis. In the positive peritoneal cytology group, 64.3% had disease outside of the uterus, while in the negative group only 12.8%. The 2-year survival rate in patients with positive peritoneal cytology was 57.1% and it was 86.4% in patients with negative peritoneal cytology. It is concluded that the findings of positive peritoneal cytology is an important prognostic factor and routine peritoneal cytology should be obtained at the time of laparotomy in patients with carcinoma of the endometrium.     

The prognostic significance of positive peritoneal cytology and adnexal/serosal metastasis in stage IIIA endometrial cancer

OBJECTIVE: The clinical significance and optimal management of patients with stage IIIA endometrial cancer are controversial. We sought to determine whether recurrence and survival of patients with stage IIIA endometrial cancer differ with surgical pathologic findings (positive peritoneal cytology versus positive adnexae or serosa) and adjuvant treatment. METHODS: Retrospective single institution analysis of patients surgically staged for IIIA endometrial cancer at Duke University Medical Center from 1973 to 2002. Stage IIIA patients were stratified into positive cytology alone (group IIIA1, n=37) and positive adnexae or uterine serosa (group IIIA2, n=20). Comparison was made with previously reported group of 467 patients with surgical stage I/II disease. Recurrence and survival were analyzed using Kaplan-Meier estimations and Cox proportional hazards model. RESULTS: Mean age of 57 patients with stage IIIA endometrial cancer was 63. Adjuvant therapies were administered to 89% patients (74% radiotherapy, 4% chemotherapy, 19% progestins). Five-year overall (OS) and recurrence-free disease-specific survival (RFDSS) were 64% and 76%, respectively. Survival was similar comparing IIIA1 (62%) and IIIA2 (68%, p=0.999). RFDSS by adjuvant therapy was: external beam radiotherapy 89% (n=10), intraperitoneal P32 84% (n=21), progestins 78% (n=9), none 75% (n=6). 61% recurrences included extrapelvic component. In multivariable analysis of stage I-IIIA patients (n=517), positive cytology but not adnexal/serosal metastasis was predictive of death (HR 1.70, 95% CI 1.06-2.73) and disease recurrence (HR 1.70, 95% CI 1.07-2.71). CONCLUSION: Among patients with stage IIIA endometrial cancer, metastasis to adnexae or serosa does not appear to confer worse prognosis than positive cytology alone. Positive cytology is an independent predictor of prognosis among patients with stage I-IIIA endometrial cancer. While optimal adjuvant therapy for these groups remains unclear, recurrence patterns suggest that systemic therapies are appropriate.     

Stage III and IV endometrial cancer: a 20-year review of patients

In advanced endometrial cancer, the importance of peritoneal cytology and optimal surgical cytoreduction remain subjects of discussion. We evaluated our clinical experience of 67 patients with FIGO stage III and IV endometrial cancer treated in the Erasmus Medical Centre in Rotterdam over a 20-year period with an emphasis on stage IIIA disease based on positive cytology only and optimal cytoreduction. Lymphadenectomy was not routinely performed and peritoneal cytology was examined in 74% of the patients. Stage IIIA disease was found in 33 patients, 10 of whom had positive cytology only. Analysis showed that incidence of recurrence and survival rates of patients with stage IIIA disease based on positive cytology only were comparable with stage IIIA disease based on other factors. In 50 patients, it was possible to remove all macroscopic tumor, whereas in 17 patients, an optimal cytoreduction was not achievable. The 2- and 5-year survival rates after optimal cytoreduction were 82.2% and 65.6%; where this could not be achieved, these figures were 50.8% and 40.6%. In advanced endometrial cancer patients, positive peritoneal cytology seems an important prognostic factor in stage IIIA disease if lymph node status is unknown. Survival is improved if optimal surgical cytoreduction is achievable.     

Prognostic significance of positive peritoneal cytology in clinical stage I adenocarcinoma of the endometrium

One hundred fifty-seven consecutive patients with clinical stage I endometrial adenocarcinoma who underwent primary surgical therapy between July 1979 and January 1986 were evaluated prospectively for malignant peritoneal cytology. No treatment was directed specifically for positive peritoneal cytology. Thirty patients (19%) had malignant peritoneal cytology. In univariate statistical analysis, positive cytology was significantly associated with depth of myometrial invasion (P = .02) and histopathology (P less than .025), but not with disease recurrence (P = .33). Recurrence developed in five (17%) of 30 patients with positive cytology and 11 (9%) of 127 patients with negative cytology. Using multivariate analysis, the presence of extrauterine disease spread other than lymph node metastasis was the only variable significantly associated with time to recurrence (P = .009). When patients with poor prognostic factors (grade 3 tumors, deep myometrial invasion, tumors larger than 2 cm, positive lymph nodes, and other extrauterine disease spread) were excluded from analysis, malignant peritoneal cytology still had no influence on time to recurrence. Of the five patients with positive peritoneal cytology who had disease recurrence, only one recurrence arose within the peritoneal cavity. The presence of positive peritoneal cytology in clinical stage I endometrial adenocarcinoma does not appear to have independent prognostic significance and probably should not influence treatment decisions in the absence of other poor prognostic factors.     

Endometrial cancer: factors affecting survival

PURPOSE: To evaluate the influence in survival of clinical and pathological findings in patients with endometrial cancer. METHODS: In 152 women treated for endometrial cancer from 1982 to 1996, personal, obstetrical and oncological data, histology, grade, myometrial invasion, peritoneal cytology, FIGO stage and treatment were correlated with survival. RESULTS: Mean age was of 60.3 +/- 11.1 years old. Eight patients had a previous history of other neoplasms (seven of them gynecological). The mean clinical complaint was abnormal uterine bleeding. The most common histological type was endometrioid (84.9%), only 51 cases did not show myometrial invasion and 119 women were in Stage I at diagnosis. Peritoneal cytology was negative in 113 patients. Seven patients out of 85 in whom lymphadenectomy was performed showed metastasis. Seventeen of the patients died. The factors influencing survival were age, myometrial invasion and lymph node metastasis. CONCLUSION: Lack of myometrial invasion, absence of lymph node metastasis and age younger than 60 years seem to be the most significant predicting factors of survival.